人類為什麼會在 80 歲左右死亡的謎團可能最終會被解開

Recently Yahoo News on-line reported the following:

Mystery of why humans die around 80 may finally be solved

Sarah Knapton

The Telegraph

Wed, April 13, 2022, 10:35 AM

The mystery of why humans die at around 80, while other mammals live far shorter or longer lives, may finally have been solved by scientists.

Humans and animals die after amassing a similar number of genetic mutations, researchers have found, suggesting the speed of DNA errors is critical in determining the lifespan of a species.

There are huge variations in the lifespan of mammals in the animal kingdom, from South Asian rats, which live for just six months, to bowhead whales, which can survive for 200 years.

Previously, experts have suggested that size is the key to longevity, with smaller animals burning up energy more quickly, requiring a faster cell turnover, which causes a speedier decline.

But a new study from the Wellcome Sanger Institute in Cambridge suggests the speed of genetic damage could be the key to survival, with long-living animals successfully slowing down their rate of DNA mutations regardless of their size.

It helps explain how a five-inch long naked mole rat can live for 25 years, about the same as a far larger giraffe, which typically lives for 24.

When scientists checked their mutation rates, they were surprisingly similar. Naked mole rats suffer 93 mutations a year and giraffes 99.

In contrast, mice suffer 796 mutations a year and only live for 3.7 years. The average human lifespan in the study was 83.6 years, but the mutation rate was far lower at around 47.

Genetic changes, known as somatic mutations, occur in all cells and are largely harmless, but some can start a cell on the path to cancer or impair normal functioning.

Dr Alex Cagan, the first author of the study, said: “To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising.

“But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate. This suggests that somatic mutations may play a role in ageing.”

The team analyzed genetic errors in the stem cells from the intestines of 16 species of mammal and found that the longer the lifespan of a species, the slower the rate at which mutations occur.

The average number of mutations at the end of lifespan across species was around 3200, suggesting there is a critical mass of errors after which a body is unable to function correctly.

 ‘Ageing is a complex process’

Although the figure differed about threefold across species the variation was far less than the variation in body size, which varied up to 40,000 fold.

The researchers believe the study opens the door to understanding the ageing process, and the inevitability and timing of death.

Dr Inigo Martincorena, the senior author of the study, said: “Ageing is a complex process, the result of multiple forms of molecular damage in our cells and tissues.

“Somatic mutations have been speculated to contribute to ageing since the 1950s, but studying them has remained difficult.

“With the recent advances in DNA sequencing technologies, we can finally investigate the roles that somatic mutations play in ageing and in multiple diseases.”

The research was published in the journal Nature.

Translation

為什麼人類會在 80 歲左右死亡，而其他哺乳動物的壽命要短得多或長得多，這一謎團可能最終被科學家們解開了。

研究人員發現，人類和動物在積累了相似數量的基因突變後死亡，這表明DNA的錯誤速度對於決定一個物種的壽命至關重要。

動物王國中哺乳動物的壽命存在巨大差異，從僅能存活 6 個月的南亞老鼠到可以存活 200 年的弓頭鯨。

此前，專家曾提出，體型是長壽的關鍵，體型較小的動物消耗能量更快，需要更快的細胞更新，從而導致更快的衰退。

但在劍橋的 Wellcome Sanger 研究所的一項新研究表明，基因損傷的速度可能是生存的關鍵，長壽動物無論它們的大小如何, 成功地減慢了 DNA 突變的速度。

這有助於解釋一隻 5 英寸長的裸鼴鼠如何能活 25 年，與通常能活 24 年的大得多的長頸鹿大致相同。

當科學家們檢查它們的突變率時，發現它們驚人地相似。裸鼴鼠每年發生 93 次突變，而長頸鹿則有 99 次。

相比之下，老鼠一年有796個突變，只能活3.7年，在研究中人類的平均壽命是83.6歲，但突變率遠低, 一年有47個左右。

被稱為體細胞突變的遺傳變化會發生在所有細胞中，並且在很大程度上是無害的，但有些可能會使細胞走上癌症之路, 或損害正常功能。

該研究的第一作者Alex Cagan博士說： “在老鼠和老虎那麽不同動物之間發現相似的基因變化模式是令人驚訝。

“但這項研究最令人興奮的方面是發現壽命與體細胞突變率成反比。這表明體細胞突變可能在衰老中起作用。”

該團隊分析了 16 種哺乳動物腸道幹細胞中的遺傳錯誤，發現一個物種的壽命越長，突變發生的速度就越慢。

跨物種壽命結束時的平均突變數量約為 3,200，這表明錯誤達臨界量之後, 身體就無法正常運作。

“老齡化是一個複雜的過程”

儘管這個數字在不同物種之間存在大約三倍的差異，但差異遠小於在體型大小的差異，後者的差異高達 40,000 倍。

研究人員認為，這項研究為了解衰老過程以及死亡的必然性和時機打開了大門。

該研究的資深作者 Inigo Martincorena 博士說： “衰老是一個複雜的過程，是我們細胞和組織中多種形式的分子損傷的結果。

“自 1950 年代以來，人們推測體細胞突變會導致衰老，但研究它們仍然很困難。

“隨著 DNA 測序技術的最新進展，我們終於可以研究體細胞突變在衰老和多種疾病中的作用。”

該研究發表在《自然》雜誌上。

So, according this this research, the average number of mutations at the end of lifespan across species was around 3,200, suggesting there is a critical mass of errors caused by genetic mutations, after which a body is unable to function correctly. This is an interesting theory.